Resorbable and biocompatible fibre glass compositions and their uses

ABSTRACT

Biocompatible and resorbable melt derived glass compositions which include: SiO 2  60-70 weight-%, Na 2 O 5-20 weight-%, CaO 5-25 weight-%, MgO 0-10 weight-%, P 2 O 5  0.5-3.0 weight-%, B 2 O 3  0-15 weight-%, Al 2 O 3  0-5 weight-%, and which contain less than 0.05 weight-% potassium. Biocompatible and resorbable glass fibres manufactured from these glass compositions, medical devices containing fibres of the invention, the use of these compositions for the manufacture of glass fibre and the use of the fibres for the manufacture of medical devices are also disclosed.

FIELD OF INVENTION

The invention relates to potassium free melt derived resorbable andbiocompatible glass compositions, fibre glass of such compositions anduse thereof for the manufacture of medical devices, as well as tomedical devices comprising such resorbable fibres.

BACKGROUND OF THE INVENTION

Various bioactive glass compositions are known in the field. They areable to bond to bone and soft tissue, and they may be used forstimulating tissue or bone growth in a mammalian body. Bioactive glassalso typically guides the formation of new tissue, which grows withinsaid glass. When bioactive glasses come into contact with aphysiological environment, a layer of silica gel is formed on thesurface of the glass. Following this reaction, calcium phosphate isdeposited to this layer and finally crystallized to a hydroxyl-carbonateapatite. Due to this hydroxyl-carbonate apatite layer the resorption ofthe bioactive glasses is slowed down when inserted into mammalianbodies.

Other types of resorbable glass compositions are also known in thefield. Resorbable glasses are not necessarily bioactive, i.e. they donot form a hydroxyl-carbonate apatite layer on the glass surface.Resorbable glass compositions are used in the glass fibre industry toresolve the problem of glass fibres ending up e.g. in lungs duringinstallation of glass fibre insulation. Disappearance of the fibres ispreferably relatively fast, so that no detrimental effects are caused tothe body. One resorbable glass composition is disclosed in EP 0 412 878.The fibres are degraded within 32 days. Such a degradation rate is,however, too fast for most medical applications, for example for screwsor pins for fixing bone defects or fractures.

EP 0 915 812 B1 and EP 1 484 292 A1 disclose biosoluble glasscomposition to improve occupational health and safety. WO 03/018496 A1discloses anti-inflammatory, wound-healing glass powder compositions.U.S. Pat. No. 6,482,444 B1 discloses silver-containing bioactive sol-gelderived glass compositions to be used in implanted materials, forpreparation of devices used for in vitro and ex vivo cell culture.

EP0802890B1 discloses a bioactive glass composition with a large workingrange. Devitrification problems are circumvented by adding potassium andoptionally magnesium to the glass.

OBJECT AND SUMMARY OF THE INVENTION

An object of the present invention is to provide a biocompatible andresorbable melt derived glass composition.

Another object of the present invention is to provide biocompatible andresorbable glass fibre.

A further object of the present invention is to provide a medicaldevice.

A still further object of the present invention is to provide use of andresorbable melt derived glass composition and fibre.

Thus the present invention provides a biocompatible and resorbable meltderived glass composition comprising:

SiO₂ 60-70 weight-%, Na₂O 5-20 weight-%, CaO 5-25 weight-%, MgO 0-10weight-%, P₂O₅ 0.5-3.0 weight-%, B₂O₃ 0-15 weight-%, Al₂O₃ 0-5 weight-%and Li₂O 0-1 weight-%,comprising less than 0.05 weight-% potassium.

The present invention also provides biocompatible and resorbable glassfibre manufactured from a biocompatible and resorbable melt derivedglass composition of the invention.

The present invention further provides a medical device comprising fibreof the invention.

The present invention still further provides use of the biocompatibleand resorbable melt derived glass composition of the invention for themanufacture of glass fibre and use of the fibres of the invention forthe manufacture of a medical device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates pH change in SBF dissolution tests as a function ofdissolution time of fibres of different fibre compositions including acomposition according to the present invention.

FIG. 2 illustrates the change of tensile strength in SBF dissolutiontests as a function of dissolution time of different fibre compositionsof the present invention.

DETAILED DESCRIPTION OF THE INVENTION Definitions

The terms used in this application, if not otherwise defined, are thoseagreed on at the consensus conference on biomaterials in 1987 and 1992,see Williams, D F (ed.): Definitions in biomaterials: Proceedings of aconsensus conference of the European Society for Biomaterials, Chester,England. Mar. 3-5, 1986. Elsevier, Amsterdam 1987, and Williams D F,Black J, Doherty P J. Second consensus conference on definitions inbiomaterials. In: Doherty P J, Williams R L, Williams D F, Lee A J(eds). Biomaterial-Tissue Interfaces. Amsterdam: Elsevier, 1992.

In this application, by bioactive material is meant a material that hasbeen designed to elicit or modulate biological activity. Bioactivematerial is often surface-active material that is able to chemicallybond with the mammalian tissues.

The term resorbable in this context means that the material isdisintegrated, i.e. decomposed, upon prolonged implantation wheninserted into mammalian body and when it comes into contact with aphysiological environment. Especially, the term resorbable glass meanssilica-rich glass that does not form a hydroxyl-carbonate apatite layeron its surface when in contact with a physiological environment.Resorbable glass disappears from the body through resorption and doesnot significantly activate cells or cell growth during its decompositionprocess.

By biomaterial is meant a material intended to interface with biologicalsystems to evaluate, treat, augment or replace any tissue, organ orfunction of the body. By biocompatibility is meant the ability of amaterial used in a medical device to perform safely and adequately bycausing an appropriate host response in a specific location. Byresorption is meant decomposition of biomaterial because of simpledissolution. By composite is meant a material comprising at least twodifferent constituents, for example an organic polymer and a ceramicmaterial, such as glass.

By melt derived glass fibre is meant glass fibre manufactured by meltingglass in a crucible at 700-1500° C. and pulling glass fibres of themolten glass through holes of the crucible, resulting in fibres with adiameter in the range of 5-300 μm (micrometers).

In the present context the term medical devices relates to any kind ofimplant used within the body, as well as devices used for supportingtissue or bone healing or regeneration. An implant according to thepresent context comprises any kind of implant used for surgicalmusculoskeletal applications such as screws, plates, pins, tacks ornails for the fixation of bone fractures and/or osteotomies toimmobilise the bone fragments for healing; suture anchors, tacks,screws, bolts, nails, clamps, stents and other devices for softtissue-to-bone, soft tissue—into-bone and soft tissue-to-soft tissuefixation; as well as devices used for supporting tissue or bone healingor regeneration; or cervical wedges and lumbar cages and plates andscrews for postero-lateral vertebral fusion, interbody fusion and otheroperations in spinal surgery. Depending on the application and purposeof the medical device material, the medical devices are expected anddesigned to be biocompatible and exhibit controlled resorption in themammalian body. The optimal resorption rate is directly proportional tothe renewal rate of the tissue in the desired implantation location. Inthe case of bone tissue, a considerable proportion of the implant ispreferably resorbed/decomposed within 6 to 14 weeks depending on theapplication, in the tissue. In cases where physical support to thehealing tissues is desirable the resorption rate might be several monthsor even several years. Furthermore, the invention can be made use of inmedical devices such as canules, catheters and stents. The invention canbe made use of in fibre reinforced scaffolds for tissue engineering.

In this specification, except where the context requires otherwise, thewords “comprise”, “comprises” and “comprising” means “include”,“includes” and “including”, respectively. That is, when the invention isdescribed or defined as comprising specified features, variousembodiments of the same invention may also include additional features.

Preferred Embodiments of the Invention

The present invention provides a slowly resorbable and biocompatiblefibre glass composition suitable for use in medical devices. Resorptionof degradable glasses is a function of composition and surface to volumeratio i.e. surface erosion by physiological environment. Due to highsurface to volume ratio of fibres, release of alkali and alkali earthmetal ions to a physiological environment can be undesirably fast. Thusit is important to know and to be able to control the resorption rate ofglass and release of alkali and alkali earth metal ions to aphysiological environment. Bioactive fibre glasses start to reactimmediately when contacted with aqueous solutions by alkali exchangereactions, i.e. sodium and potassium ions in the glass are replaced byhydrogen ions from the solution. A rapid and high degree of dissolutionwill locally increase the pH of surrounding interstitial fluid, in spiteof its buffering capacity, to undesirably high values. Further, bodyfluids contain a relatively high content of sodium but a low content ofpotassium ions. Thus, rapid leaching of potassium ions from glasses islikely to have a much higher relative influence on the local body fluidcomposition than leaching of sodium ions, i.e. alkali metal ions areresponsible for a high local detrimental pH increase and also in certaincases potassium may cause physiological problems through neurotoxic andcytotoxic effects

Now it has been surprisingly found out that omitting potassium from themelt derived glass fibre compositions will increase biocompatibility andeliminate neurotoxic and cytotoxic effects. Potassium plays an importantrole in muscle contraction and nerve transmission. Muscle and nervecells have specialized channels for moving potassium in and out of thecell. It is well known in the art that when increased amounts ofpotassium is in the extracellular matrix in tissues the cells of, e.g.muscles and nerves can be damaged, i.e. can be toxic to human tissues.

Furthermore, by varying the amount of silica and other components i.e.Na₂O, CaO, MgO, P₂O₅, B₂O₃, and Al₂O₃ in the glass composition presentedin this invention, the resorption rate of the glass fibres can be easilycontrolled and tailor-made for diverging end applications.

According to one aspect of the present invention the amounts of SiO₂ andNa₂O are important features and should be kept at quantities preferablybetween 60 and 70 weight-% and between 5 and 20 weight-% respectively tosustain resorbability of the glass fibre without giving rise to highamounts of released alkali metals thus preventing a detrimental ortoxicological local pH peak in a physiological environment. In addition,in order to retain long term bioactivity i.e. CaP formation of theglass, fibres phosphorous and calcium oxides are required in sufficientamounts. Moreover, aluminium and boric oxide can be used to reducesolubility, and magnesium oxide can be added to increase elasticity andenhance the fibre formation from melt.

A typical potassium free, i.e. comprising at most only minute amounts ofpotassium, resorbable melt derived glass composition suitable for thepresent invention comprises

SiO₂ 60-70 weight-%, Na₂O 5-20 weight-%, CaO 5-25 weight-%, MgO 0-10weight-%, P₂O₅ 0.5-3.0 weight-%, B₂O₃ 0-15 weight-%, Al₂O₃ 0-5 weight-%and Li₂O 0-1 weight-%

Although the glass composition is potassium free, it may includepotassium, e.g. as an impurity from raw materials, but not more than0.05 weight-%, preferably not more than 0.03 weight-%, more preferablynot more than 0.01 weight-% and most preferably not more than 0.005weight-%. Potassium is preferably excluded and should be avoided even asan impurity.

Many preferred compositions of the invention comprise

SiO₂ 62-68 weight-%, Na₂O 10-15 weight-%, CaO 8-20 weight-%, MgO 0-10weight-%, P₂O₅ 0.5-3 weight-%, B₂O₃ 0-4 weight-% and Al₂O₃ 0-2.5 weight.

Many other preferred compositions of the invention comprise

SiO₂ 62-68 weight-%, Na₂O 10-15 weight-%, CaO 10-20 weight-%, MgO 0-10weight-%, P₂O₅ 0.5-3 weight-%, B₂O₃ 1.3-4 weight-% and Al₂O₃ 0-2.5weight

Some preferred compositions of the invention comprise

SiO₂ 62-68 weight-%, Na₂O 10-15 weight-%, CaO 8-20 weight-%, MgO 0-6weight-%, P₂O₅ 0.5-3 weight-%, B₂O₃ 0-4 weight-% and Al₂O₃ 0-2.5 weight.

Some other preferred compositions of the invention comprise

SiO₂ 64-66 weight-%, Na₂O 5-10 weight-%, CaO 11-18 weight-%, MgO 2-8weight-%, P₂O₅ 0.5-3 weight-%, B₂O₃ 0-5 weight-% and Al₂O₃ 0-1.0 weight.

Some further preferred compositions of the invention comprise

SiO₂ 64-66 weight-%, Na₂O 5-10 weight-%, CaO 12-18 weight-%, MgO 2-6weight-%, P₂O₅ 0.5-3 weight-%, B₂O₃ 0-3 weight-%, and Al₂O₃ 0-1.0weight-%.

Resorbable and biocompatible melt derived glass fibres of the presentinvention are manufactured from resorbable glass compositions accordingto the invention. Preferred fibres according to the invention aremanufactured from preferred compositions of the invention.

The time for typical fibres of the invention to be fully resorbed invitro in simulated body fluid (SBF), calculated using a resorption ratedetermined by dissolution in sink at +37° C. using the linear portion ofthe resorption curve, is 1-100, preferably 2-45, more preferably 3-15,even more preferably 4-70, still more preferably 5-30 and mostpreferably 6-15 months.

The thickness of typical fibres of the invention is <300 μm, preferably1-75 μm, more preferably 5-30 μm, even more preferably 10-25 μm, stillmore preferably 10-20 μm and most preferably about 15 μm.

The tensile strength of typical fibres of the invention is 0.7-3 GPa,preferably 0.9-2.5 GPa, more preferably 1.0-2.0 GPa and most morepreferably 1.5-2.0 GPa.

The tensile strength of other typical fibres of the invention is 0.6-2GPa, preferably 0.9-1.8 GPa, more preferably 1.0-1.6 GPa and most morepreferably 1.1-1.5 GPa.

Medical devices according to the invention comprise fibres of theinvention. Preferred medical devices according to the present inventioncomprise preferred fibres of the invention.

Many preferred devices according to the invention are fully based on orcomprise chopped and/or continuous fibre of the invention; and/or anykind of textile, woven or non-woven comprising fibre according of theinvention.

Typical medical devices of the invention are any kind of implants usedwithin the body, preferably selected from the group consisting of ajoint implant, an internal/external fixation device, a stent a, pin, anail, a screw, a spike, a stud, a plate, and a device for supportingtissue or bone healing and/or regeneration.

In some preferred embodiments of medical devices of the invention theamount of fibre according to the invention is >10 volume-%,preferably >40 volume-%, more preferably >60 volume-%, mostpreferably >90 volume-% of the total volume of the fibres of saidmedical device.

In some preferred embodiments of the invention the fibres are embeddedin a continuous polymer matrix. Preferably the polymer matrix comprisesat least one polymer selected from the group consisting of polyglycolide(PGA); copolymers of glycolide, such as glycolide/L-lactide copolymers(PGA/PLLA), glycolide/tri-methylene carbonate copolymers (PGA/TMC);polylactides (PLA); stereocopolymers of PLA, such as poly-L-lactide(PLLA), poly-DL-lactide (PDLLA), L-lactide/DL-lactide copolymers; othercopolymers of PLA, such as lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/d-valerolactonecopolymers, lactidek-caprolactone copolymers; terpolymers of PLA, suchas lactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolidek-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically 3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates, such aspolyhydroxybutyrates (PHB); PHB/b-hydroxy-valerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone; poly-ε-caprolactone; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinyl-alcohol (PVA); polypeptides; poly-b-malic acid (PMLA);poly-b-alkanoic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides) and mixtures or thermosets thereof; andpreferably selected from the group consisting of poly(ε-caprolactone),poly(ε-caprolactone-l-lactide) copolymers, polylactide-co-glycolide andpolylactide.

Fibres as such or comprised in the medical devices are resorbable andbiocompatible when exposed to a physiological environment.

The above mentioned glass compositions are manufactured according to astandard melt processes known in the art, except for a certainlimitation that is included in the fibre glass manufacturing process.Special focus is required on raw material purity, particle sizedistribution, homogeneity derived from the sequence of melting, crushingand re-melting process. A homogeneous glass preform, manufactured by themelt process, is then drawn to fibre according to process described inpatent application EP1958925A1. Because resorbable and bioactive glasseshave a strong tendency to transfer from the amorphous glass state to thecrystalline state when heating glass proprietary technology, e.g.technology disclosed in patent application EP1958925A1 enabling themanufacture of a wide range of resorbable and bioactive glassescircumventing problems relating to crystallization during fibreproduction, to produce fibres is preferably used.

It is known for the persons skilled in the art that most biodegradableglass compositions are unsuitable for melt derived fibre drawing due tocrystallization properties, melt viscosity properties and melt strength.It has been surprisingly discovered in this invention that the abovementioned compositions are feasible for fibre drawing also in industrialscale with the method described in patent application EP1958925A1 eventhough the composition lacks the fibre drawing facilitating (andcytotoxic) component K₂O. The fibres show improved strength properties,when compared for example to polymer fibres having the same diameter.According to one embodiment of the invention, suitable glass fibresnormally show a tensile strength of 700 MPa-3 GPa, more typically 900MPa-2.5 GPa, preferably 1.0-2.0 GPa, more preferably 1.5-2.0 GPa.Comparable polymer fibres have typically a tensile strength of 300-600MPa. Modulus for glass fibres is typically 50-100 GPa, more typically60-80 GPa, preferably 65-75 GPa.

The advantage of the medical devices according to the present inventionis that they disappear from the body by degradation without giving riseto toxic effects through the release of potassium and/or a high localpH.

Another advantage of the medical devices according to the invention istheir strength and feasibility of manufacture. A medical deviceaccording to the present invention can be manufactured by arranging thefibres with a polymer matrix, preferably with a resorbable polymermatrix, and using any type of polymer processing equipment, e.g. open orclosed batch mixer or kneader, continuous stirring tank reactor ormixer, extruder, injection moulding machine, RIM, tube reactor or otherstandard melt processing or melt mixing equipment known in the field,producing and/or shaping the arranged fibres with the polymer matrixinto an implant having a desired orientation of the continuous fibresand/or chopped/cut fibres and/or woven, non-woven mats/textiles. Oneadvantage of the present invention is that the melting temperature ofthe matrix material is around 30-300° C., and the glass transitiontemperature of the fibres around 450-650° C. Consequently, the glassfibres are not damaged by the temperature of the melted matrix materialand a strong fibre reinforced medical device is obtained when the matrixis let to solidify. The implants according to the present invention canalso be manufactured by using any type of polymer processing equipment,e.g. open or closed batch mixer or kneader, continuous stirring tankreactor or mixer, extruder, injection molding machine, RIM, tubereactor, or other standard melt processing or melt mixing equipmentknown in the field.

The glass composition according to the present invention is, in additionto being resorbable, also biocompatible. It can thus be implanted inmammals, such as humans, and it does not react in an undesirable manner,cause any side effects or reject the surrounding tissues.

The resorption rate of the resorbable glass composition according to thepresent invention is normally 1-100, 3-30, 4-80, 5-45, 6-20, sometimes8-16 months, which resorption rates are sufficient for medicalapplications. For example, a typical resorption rate for an anteriorcruciate ligament screw is 3-24 months, the silica content of thecomposition then being approximately from 60 to 65 weight-%. The typicalresorption rate is 12-24 months when the composition is used for medicaldevices suitable for internal fixation devices, the silica content ofthe composition then being approximately from 66 to 70 weight-%.

The resorption rate or degradation can be measured by measuring thesilica ion concentration dissolved at certain immersion times in aqueoussolution. A method suitable for measuring resorption rates, i.e. glassfibre disintegration, is disclosed for example in J. Korventausta etal., Biomaterials, Vol. 24, Issue 28, December 2003, pp. 5173-5182.Another way to measure degradation is to monitor weight loss, pH changeand mechanical strength loss in aqueous solution.

The present invention also relates to resorbable and biocompatible glassfibres manufactured from resorbable and biocompatible glass compositionsas defined above. All the features and embodiments listed above inconnection with the suitable resorbable and biocompatible glasscompositions apply mutatis mutandis to the suitable fibres and to themedical devices according to the present invention.

According to one embodiment of the invention the thickness of the fibressuitable for the present invention is <300 μm, typically 1-75 μm, moretypically 5-30 μm, preferably 10-25 μm, more preferably 10-20 μm,usually approximately 15 μm. The fibres can be used as long singlefibres, as yarns, braids, rovings, and bands or as different types offabrics made by using the methods of textile technology.

The fibres can also be used as chopped fibres and mats or textilesmanufactured from chopped fibre. For example, according to oneembodiment of the invention fibres having a diameter <300 μm, typically1-75 μm, more typically 5-30 μm, preferably 10-25 μm, more preferably10-20 μm, usually approximately 15 μm can be used as chopped fibres.Chopped fibres can be used also for preparing non-woven textile-likematerials. These non-woven textiles can be combined with resorbableplastics and can be used for example for the manufacture of hot mouldedimplants. Chopped fibres can also be used to reinforce implants that aremanufactured by injection moulding or other processing techniques knownin the field of polymer processing.

According to one embodiment of the invention the length of the choppedfibres is <20 mm, typically 0.5-10 mm, more typically 1-5 mm, preferably3-5 mm, usually approximately 5 mm. According to another embodiment ofthe invention the length of the continuous fibres is >20 mm,preferably >30 mm, usually more than 40 mm or most preferably as fullycontinuous fibre in pultrusion as an example.

The resorbable glass composition suitable for the present invention canbe used for manufacturing various medical devices. Such devices can beused to support and strengthen the defect site during healing, and canform part of the tissue once the defect is healed. Due to the long termbioactivity of some of the compositions mentioned above the tissue maygrow within the resorbable material and function as a tissueregenerating scaffold.

The medical device according to the present invention comprises apolymer matrix, preferably a continuous polymer matrix, but notexcluding discontinuous polymer matrix, which polymer matrix isnaturally biocompatible. Said biocompatible polymer matrix may be andpreferably is also resorbable, however not excluding biostablebiocompatible polymers.

The resorbable glass fibres are preferably embedded in a continuouspolymer matrix, which means that the surfaces of the fibres are coveredby said polymer. Preferably, at least 80% of the surfaces of the fibresare covered by the polymer matrix, more preferably at least 90%, andmost preferably at least 95% of the surface of the fibres is covered bythe polymer matrix. Preferably also at least 99% of the fibres of thesurface of the medical device are covered by the polymer matrix.

According to the present invention the fibres can be used as loadbearing component embedded a degradable matrix in a tissue engineeringmedical device with or without higher bioactivity and resorption ratecontaining degradable glass, which can be in form of granules, spheres,blocks and fibres.

According to the present invention the fibres can be used as a bioactivecomponent embedded in a degradable matrix in a porous tissue engineeringscaffold. Preferably, the scaffold has a porosity degree of 60%, morepreferably at least 80%, and most preferably at least 90%.

The polymer matrix material of the medical device according to thepresent invention may be selected from the group consisting ofbiocompatible polymers, such as polymers of methacrylic acid, acrylicacid and vinylpyrrolidone, polyolefins, polyalkylene oxides,polyvinylalcohol, polylactones, polycarbonates, poly-anhydrides,aliphatic polyesters, polyamides, polyimides, liquid crystal polymers,polyorthoesters, copolymers of the above mentioned and thermosets ofabove mentioned polymers, polymers and copolymers based on units derivedfrom hydroxyacids and natural polymers, such as sugars, starch,cellulose and cellulose derivatives, polysaccharides, collagen,chitosan, fibrin, hyalyronic acid, polypeptides and proteins.

The polymer matrix material may thus be either a biostable or aresorbable material. The material can be porous or it can become porousduring the use and/or when in contact with the tissue. Biostablepolymers do not dissolve or react in contact with body fluids or tissue.Some suitable biostable polymers are derivatives of acrylic acid ormethacrylic acid, such as methyl(methacrylate). Some suitable resorbablepolymers are homo- and copolymers of lactones and lactides andpolycarbonates. The polymer may be a biodegradable and/or bioresorbablepolymer and/or a biopolymer, preferably derived from hydroxyl acidunits, a preferred polymeric material beingpoly(ε-caprolactone-l-lactide) copolymer or poly(ε-caprolactone) orpoly(dl-lactide) or poly(l-lactide) or poly(l-lactide-co-glycolide).Mixtures of any of the above-mentioned polymers and their various formsmay also be used. For some embodiments also gutta-percha may be used.

According to one embodiment of the invention also following resorbablepolymers, copolymers and terpolymers may be used as matrix material:polyglycolide (PGA); copolymers of glycolide, glycolide/trimethylenecarbonate copolymers (PGA/TMC); other copolymers of PLA, such aslactide/tetramethylglycolide copolymers, lactide/trimethylene carbonatecopolymers, lactide/d-valerolactone copolymers, lactidek-caprolactonecopolymers; terpolymers of PLA, such as lactide/glycolide/trimethylenecarbonate terpolymers, lactide/glycolidek-caprolactone terpolymers,PLA/polyethylene oxide copolymers; polydepsipeptides; unsymmetrically3,6-substituted poly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates, suchas polyhydroxybutyrates (PHB); PHB/b-hydroxyvalerate copolymers(PHB/PHV); poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-caprolactone; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA);poly-b-alkanoic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and thermosets of abovementioned polymers.

The medical device according to the present invention may also comprisebioactive glass fibres, such as fibres made of compositions disclosed inEP 080 2890 and EP 1405 647. The medical device may also comprisepolymer fibres, such as fibres of any of the polymers mentioned above inconnection with the polymer matrix. However, the amount of resorbableglass fibres is usually >10 volume-%, preferably >40 volume-%, morepreferably >60 volume-%, most preferably >90 volume-% of the totalvolume of the fibres of the medical device.

According to still another embodiment of the present invention themedical device may comprise two or more types of resorbable fibres, eachtype having a different composition. The medical device may alsocomprise two or more groups of fibres having different median diameter.It is also possible that all of the fibres of the medical device do nothave the same diameter, but the diameter may vary as desired.

All the fibres used in the medical devices according to the presentinvention may be in various forms such as continuous fibres or choppedfibres. Their orientation can also be freely chosen depending on themedical device in which they are used and in function of the intendeduse.

EXAMPLES

Embodiments of the present invention will now be described in moredetail in the following examples. The examples are illustrative but notlimiting the compositions, methods and applications of the presentinvention, which are obvious to those skilled in the art.

General manufacture of a biodegradable glass preform was made accordingto the following procedure: dry-mix of raw materials, melting inpt-crucible in furnace, annealing, crushing, re-melting and annealingfrom following raw material sources: SiO₂, Al₂O₃, Na₂CO₃, (CaHPO₄)(H₂O),CaCO₃, H₃BO₃ and MgO. Fibre drawing was conducted according to method inpatent application EP1958925A1.

Example 1 Glass Fibre Compositions Manufactured for a pH Study

According to the general procedure the following compositions were usedfor preform and fibre manufacturing for a pH study:

Glass Resorption code Na₂O K₂O MgO CaO B₂O₃ P₂O₅ SiO₂ rate FL107 10 0 616 2 2 64 Slow FL207 5 5 6 16 2 2 64 Slow FL307 5 10 3 22 2 2 56 FastFL407 10 5 3 22 2 2 56 Fast S59 25.5 0 0 11 1.3 2.5 59.7 Medium-fast13-93 6 12 5 20 0 4 53 Fast 1-98 6 11 5 22 1 2 53 Fast

The average fibre diameter was deducted to 35 μm by SEM images of fibrecross sections. Cut (16 mg) fibres were immersed in 16 ml simulated bodyfluid [SBF by Kokubo et.al. J. Biomed. Mater. Res. 24 (1990), p. 72],i.e. under in sink conditions. These values gave roughly the surfacearea to the volume of SBF ratio 0.4 cm⁻¹. The immersion time intervalsused were between 4 and 72 hours. The samples were kept in a water bathat 37° C. After separating the samples from the SBF, the final pH of thesolution was measured and the pH change during first 72 h is shown inFIG. 1.

The pH increase for the slowly reacting glass fibres FL107, FL207, andmedium-fast S59, was minimal during the first four hours. No clearincrease in pH can be deduced from the results. In contrast, the pH ofthe other glasses had increased already during this time interval. ThepH increased linearly for the slow glasses during the first 72 h, whilethe pH of the fast glasses increased more rapidly during first 24 h,after which the pH increase rate slowed down. This suggests that areaction layer formation of calcium phosphates started for the fastglasses already after 24 h thereby forming a diffusion barrier betweenthe solution and glass. The pH continued to increase linearly for theslow glasses up to one week after which the rate decreased. Thedecreased rate suggests that the CaP layer formation has initiated, andthus acted as a protective layer against leaching.

Example 2

In Vitro Testing of a Fast Resorption Rate Potassium Containing FibreGlass Composition 1-98 with Stem Cells

A fast resorbable potassium containing fibre glass composition 1-98,presented above in example 1, was tested in vitro with human adiposestem cells cultured in DMEM-F12 supplemented with 10% foetal bovineserum (FBS), 1% antibiotic/antimocotic and 1% L-glutamine at 37° C. in ahumidified 5% CO₂ atmosphere. Before combining fibre glass 1-98 andcells, the fibre glass was first washed three times with the cell growthmedium and then incubated with cell growth medium for 48 hours. Cellviability was tested using a non-quantitative dead/alive stainingmethod.

The result of cell viability testing was the following:

-   -   a notable and rapid increase of cell growth medium pH    -   almost all the cells died when cultured for three days on 1-98        fibre glass    -   few living cells that were growing on the fibre surface had        abnormal morphology, indicated by green cytoplasmic staining

Example 3

Slow Resorbable and Biocompatible Fibre Glass with Aluminium and LowPhosphorous Content

According to the general procedure the following composition was usedfor preform and fibre manufacturing:

SiO₂ 64.0 weight-%, Na₂O 11.0 weight-%, CaO 18.0 weight-%, B₂O₃ 2.0weight-% MgO 2.0 weight-% P₂O₅ 0.5 weight-%, Al₂O₃ 2.5 weight-%,

After drawing the fibres were stored in foil bags under protective gasand stored for further analyses and use. The composition and amorphousnature was confirmed using XRF and XRD, respectively. The average fibrediameter was around 35 μm.

Example 4

Slow Resorbable and Biocompatible Fibre Glass with High Silicon Content

According to the general procedure the following composition was usedfor preform and fibre manufacturing:

SiO₂ 65.5 weight-%, Na₂O 12.0 weight-%, CaO 18.0 weight-%, P₂O₅ 1.5weight-%, B₂O₃ 2.0 weight-%, MgO 1.0 weight-%

After drawing the fibres were stored in foil bags under protective gasand stored for further analyses and use. The composition and amorphousnature was confirmed using XRF and XRD, respectively. The average fibrediameter was around 35 μm.

Example 5

Slow Resorbable and Biocompatible Fibre Glass with High Sodium andMagnesium Content

According to the general procedure the following composition was usedfor preform and fibre manufacturing:

SiO₂ 64.0 weight-%, Na₂O 16.0 weight-%, CaO 14.0 weight-%, P₂O₅ 1.0weight-%, B₂O₃ 1.5 weight-%, MgO 3.5 weight-%

After drawing the fibres were stored in foil bags under protective gasand stored for further analyses and use. The composition and amorphousnature was confirmed using XRF and XRD, respectively. The average fibrediameter was around 35 μm.

Example 6

Slow Resorbable and Biocompatible Fibre Glass with Low Sodium and HighCalcium Content

According to the general procedure the following composition was usedfor preform and fibre manufacturing:

SiO₂ 61.0 weight-%, Na₂O 10.0 weight-%, CaO 22.0 weight-%, P₂O₅ 3.0weight-%, B₂O₃ 1.0 weight-%, MgO 3.0 weight-%

After drawing the fibres were stored in foil bags under protective gasand stored for further analyses and use. The composition and amorphousnature was confirmed using XRF and XRD, respectively. The average fibrediameter was around 35 μm

Example 7

Slow Resorbable and Biocompatible Fibre Glass Composition with LowCalcium and High Silicon Content

According to the general procedure the following composition wasmanufactured for preform and fibre manufacturing:

Glass code Na₂O K₂O MgO CaO B₂O₃ P₂O₅ SiO₂ Al₂O₃ NX-3 11.8 0 6.0 8.0 2.71.5 70.0 0 NX-4 12.0 0 3.1 12.0 1.1 1.5 69.8 0.5 NX-8 14.0 0 5.4 9.0 2.31.5 67.8 0 NX-12 17.5 0 2.0 10.0 0 0.5 70.0 0

Example 8

Physical properties of glass melt of selected resorbable andbiocompatible potassium free glass fibre compositions

Physical properties (i.e. melt viscosity) was measured with hightemperature rotational viscometer for selected resorbable andbiocompatible potassium free glass fibre compositions:

Glass code Na₂O K₂O MgO CaO B₂O₃ P₂O₅ SiO₂ Al₂O₃ NC-02 11.0 0 2.0 18.02.0 0.5 64.0 2.5 NC-021 11.0 0 2.0 18.0 2.0 0 64.5 2.5 Viscosity [dPas]1.5 2 2.5 3 3.5 Temp NC-02 [° C.] 1470 1323 1207 1113 1035 Temp NC-021[° C.] 1443 1320 1203 1112 1037

Example 9

Comparison of tensile properties of selected resorbable andbiocompatible potassium free glass fibres against commercial E-glass

Comparison of the single glass fibre tensile behaviour, Favigraphsemi-automatic fibre tensile tester equipped with 1N load cell was used,according to DIN EN IS05079 and DIN 53835-2. The tensile test wasconducted with gauge length of 50 mm and a cross head speed of 0.2mm/min. Comparison was conducted between resorbable and biocompatiblepotassium free glass fibres against commercial E-glass fibremanufactured with same method and results presented as mean value from50 parallel samples.

Glass code Na₂O K₂O MgO CaO B₂O₃ P₂O₅ SiO₂ Al₂O₃ NC-02 11.0 0 2.0 18.02.0 0.5 64.0 2.5 NC-021 11.0 0 2.0 18.0 2.0 0 64.5 2.5 Diameter TensileTest Young's modulus Strain Glass code [μ] [MPa] [GPa] [%] NC-02 13.92064 79.39 2.8 NC-021 14.5 990 74.34 1.4 E-glass 15.6 1069 72.43 1.5

Example 10 Resorption of Glass Fibres as a Function of MechanicalStrength by Dissolution in Simulated Body Fluid (SBF)

According to general procedure following compositions were used forpreform and fibre manufacturing:

Glass code Na₂O K₂O MgO CaO B₂O₃ P₂O₅ SiO₂ Al₂O₃ S59 25.5 0 0 11.0 1.32.5 59.7 0 NC-02 11.0 0 2.0 18.0 2.0 0.5 64.0 2.5 NC-06 12.0 0 1.0 18.02.0 1.5 65.5 0 NC-07 16.0 0 3.5 14.0 1.5 1.0 64.0 0 NC-09 10.0 0 3.022.0 1.0 3.0 61.0 0 NC-10 10.0 0 6.0 16.0 1.0 3.0 64.0 0

Resorption of glass fibres were measured by loss of mechanical strengthin SBF dissolution. Dissolution study was performed by immersing thefibres to SBF and the samples were withdrawn from after 0, 7 and 14 daysand analysed. The tensile testing of fibres was done according to theASTM C 1557-03 standard. The tensile strength is calculated from theratio of the peak force and the cross-sectional area of the fibre.

Tensile strength results as a function of dissolution time are presentedin FIG. 2. The results show that fast degradable fibre glass compositionS59 lost its strength rapidly already after 7 days immersion time in SBFcompared to glass fibre compositions according to the present invention.

Other Preferred Embodiments

It will be appreciated that the compositions, fibres, medical devicesand uses of the present invention can be incorporated in the form of avariety of embodiments, only a few of which are disclosed herein. Itwill be apparent for the expert skilled in the field that otherembodiments exist and do not depart from the spirit of the invention.Thus, the described embodiments are illustrative and should not beconstrued as restrictive.

1. A biocompatible and resorbable melt derived glass compositioncomprising: SiO₂ 60-70 weight-%, Na₂O 5-20 weight-%, CaO 5-25 weight-%,MgO 0-10 weight-%, P₂O₅ 0.5-3.0 weight-%, B₂O₃ 0-15 weight-%, Al₂O₃ 0-5weight-% and

comprising less than 0.05 weight-% potassium.
 2. The compositionaccording to claim 1 comprising less than 0.03 weight-% and preferablyless than 0.01 weight-%, and most preferably less than 0.005 weight-%potassium.
 3. The bioactive composition according to claim 1 or 2characterized in that the composition comprises SiO₂ 62-68 weight-%,Na₂O 10-15 weight-%, CaO 8-20 weight-%, MgO 0-10 weight-%, P₂O₅ 0.5-3weight-%, B₂O₃ 0-4 weight-% and Al₂O₃ 0-2.5 weight-%.


4. The composition according to claim 1 or 2 characterized in that thecomposition comprises SiO₂ 64-66 weight-%, Na₂O 5-10 weight-%, CaO 10-15weight-%, MgO 2-6 weight-%, P₂O₅ 0.5-3 weight-%, B₂O₃ 0-3 weight-%, andAl₂O₃ 0-1.0 weight-%.


5. Biocompatible and resorbable glass fibre manufactured from abiocompatible and resorbable melt derived glass composition according toany of claims 1 to
 4. 6. Fibre according to claim 5 characterized inthat the time for the fibre to be fully resorbed in vitro in simulatedbody fluid (SBF), calculated using a resorption rate determined bydissolution in sink at +37° C. using the linear portion of theresorption curve, is 1-100, preferably 2-45, more preferably 3-15, evenmore preferably 4-70, still more preferably 5-30 and most preferably6-15 months.
 7. Fibre according to claim 5 or 6, characterized in thatthe thickness of the fibre is <300 μm, preferably 1-75 μm, morepreferably 5-30 μm, even more preferably 10-25 μm, still more preferably10-20 μm and most preferably about 15 μm.
 8. Fibre according to claim 5,6 or 7 characterized in that the tensile strength of the fibre is 0.7-3GPa, preferably 0.9-2.5 GPa, more preferably 1.0-2.0 GPa and mostpreferably 1.5-2.0 GPa.
 9. A medical device comprising fibre of any ofclaims 5 to
 8. 10. The medical device according to claim 9,characterized in that the device is fully based on or comprises choppedand/or continuous fibre according to any of claims 5 to 8; and/or anykind of textile, woven or non-woven comprising fibre according to any ofclaims 5 to
 8. 11. The medical device according to claim 9 or 10characterized in that device is any kind of implant used within thebody, preferably selected from the group consisting of a joint implant,an internal/external fixation device, a stent a, pin, a nail, a screw, aspike, a stud, a plate, and a device for supporting tissue or bonehealing and/or regeneration.
 12. The medical device according to claim9, 10 or 11 characterized in that the amount of fibre according to anyof claims 4 to 7 is >10 volume-%, preferably >40 volume-%, morepreferably >60 volume-%, most preferably >90 volume-% of the totalvolume of the fibres of said medical device.
 13. The medical deviceaccording to any of claims 9 to 12 characterized in that the fibres areembedded in a continuous polymer matrix.
 14. The medical deviceaccording to claim 13 characterized in that the polymer matrix comprisesat least one polymer selected from the group consisting of polyglycolide(PGA); copolymers of glycolide, such as glycolide/L-lactide copolymers(PGA/PLLA), glycolide/trimethylene carbonate copolymers (PGA/TMC);polylactides (PLA); stereocopolymers of PLA, such as poly-L-lactide(PLLA), poly-DL-lactide (PDLLA), L-lactide/DL-lactide copolymers; othercopolymers of PLA, such as lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/d-valerolactonecopolymers, lactide/ε-caprolactone copolymers; terpolymers of PLA, suchas lactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolidek-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically 3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxy-alkanoates, such aspolyhydroxybutyrates (PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone; poly-ε-caprolactone; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinyl-alcohol (PVA); polypeptides; poly-b-malic acid (PMLA);poly-b-alkanoic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides) and mixtures or thermosets thereof; andpreferably selected from the group consisting of poly(ε-caprolactone),poly(ε-caprolactone-l-lactide) copolymers, polylactide-co-glycolide andpolylactide.
 15. Use of the biocompatible and resorbable melt derivedglass composition according to any of claims 1 to 4 for the manufactureof glass fibre.
 16. Use of the fibres according to any of claims 5 to 8for the manufacture of a medical device.